Andrew James Thomas Stevenson

Efficient neuroplasticity induction in chronic stroke patients by an associative brain-computer interface

Brain-computer interfaces (BCIs) have the potential to improve functionality in chronic stoke patients when applied over a large number of sessions. Here we evaluated the effect and the underlying mechanisms of three BCI training sessions in a double-blind sham-controlled design. The applied BCI is based on Hebbian principles of associativity that hypothesize that neural assemblies activated in a correlated manner will strengthen synaptic connections. Twenty-two chronic stroke patients were divided into two training groups. Movement-related cortical potentials (MRCPs) were detected by electroencephalography during repetitions of foot dorsiflexion. Detection triggered a single electrical stimulation of the common peroneal nerve timed so that the resulting afferent volley arrived at the peak negative phase of the MRCP (BCIassociative group) or randomly (BCInonassociative group). Fugl-Meyer motor assessment (FM), 10-m walking speed, foot and hand tapping frequency, diffusion tensor imaging (DTI) data, and the excitability of the corticospinal tract to the target muscle [tibialis anterior (TA)] were quantified. The TA motor evoked potential (MEP) increased significantly after the BCIassociative intervention, but not for the BCInonassociative group. FM scores (0.8 ± 0.46 point difference, P = 0.01), foot (but not finger) tapping frequency, and 10-m walking speed improved significantly for the BCIassociative group, indicating clinically relevant improvements. Corticospinal tract integrity on DTI did not correlate with clinical or physiological changes. For the BCI as applied here, the precise coupling between the brain command and the afferent signal was imperative for the behavioral, clinical, and neurophysiological changes reported. This association may become the driving principle for the design of BCI rehabilitation in the future. Indeed, no available BCIs can match this degree of functional improvement with such a short intervention.

Interlimb communication to the knee flexors during walking in humans

•  Following unexpected ipsilateral knee extension joint rotations applied during the late stance phase of the gait cycle in humans, a crossed reflex response was observed in the contralateral biceps femoris (cBF) muscle with a mean onset latency of 76 ms. •  Transcranial magnetic and electrical stimulation applied to the primary motor cortex revealed that a transcortical pathway probably contributes to the cBF response. •  We hypothesize that the cBF response signifies a preparation of the contralateral leg for early load bearing, helping the body to maintain dynamic stability during walking. •  This is the first study to show that a transcortical pathway contributes to an interlimb reflex in upper leg muscles. The transcortical nature of the response may allow for more adaptable responses than purely spinally mediated reflexes due to integration with other sensory information.

Interlimb communication following unexpected changes in treadmill velocity during human walking

Interlimb reflexes play an important role in human walking, particularly when dynamic stability is threatened by external perturbations or changes in the walking surface. Interlimb reflexes have recently been demonstrated in the contralateral biceps femoris (cBF) following knee joint rotations applied to the ipsilateral leg (iKnee) during the late stance phase of human gait (Stevenson AJ, Geertsen SS, Andersen JB, Sinkjær T, Nielsen JB, Mrachacz-Kersting N. J Physiol 591: 4921-4935, 2013). This interlimb reflex likely acts to slow the forward progression of the body to maintain dynamic stability following the perturbations. We examined this hypothesis by unexpectedly increasing or decreasing the velocity of the treadmill before (-100 and -50 ms), at the same time, or following (+50 ms) the onset of iKnee perturbations in 12 healthy volunteers. We quantified the cBF reflex amplitude when the iKnee perturbation was delivered alone, the treadmill velocity change was delivered alone, or when the two perturbations were combined. When the treadmill velocity was suddenly increased (or decreased) 100 or 50 ms before the iKnee perturbations, the combined cBF reflex was significantly larger (or smaller) than the algebraic sum of the two perturbations delivered separately. Furthermore, unexpected changes in treadmill velocity increased the incidence of reflexes in other contralateral leg muscles when the iKnee perturbations were elicited alone. These results suggest a context dependency for interlimb reflexes. They also show that the cBF reflex changed in a predictable manner to slow the forward progression of the body and maintaining dynamic stability during walking, thus signifying a functional role for interlimb reflexes.

The effect of type of afferent feedback timed with motor imagery on the induction of cortical plasticity

A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain-computer interface (BCI) intervention into the clinical setting requires that the proprioceptive input is comparable to the techniques implemented during the rehabilitation process. These consist mainly of functional electrical stimulation (FES) and passive movement induced by an actuated orthosis. In this study, we compared these two interventions (BCIFES and BCIpassive) where the afferent input was timed to arrive at the motor cortex during the PN of the MRCP. Twelve healthy participants attended two experimental sessions. They were asked to perform 30 dorsiflexion movements timed to a cue while continuous electroencephalographic (EEG) data were collected from FP1, Fz, FC1, FC2, C3, Cz, C4, CP1, CP2, and Pz, according to the standard international 10-20 system. MRCPs were extracted and the PN time calculated. Next, participants were asked to imagine the same movement 30 times while either FES (frequency: 20Hz, intensity: 8-35mAmp) or a passive ankle movement (amplitude and velocity matched to a normal gait cycle) was applied such that the first afferent inflow would coincide with the PN of the MRCP. The change in the output of the primary motor cortex (M1) was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior (TA) muscle and measuring the motor evoked potential (MEP). Spinal changes were assessed pre and post by eliciting the TA stretch reflex. Both BCIFES and BCIpassive led to significant increases in the excitability of the cortical projections to TA (F(2,22)=4.44, p=0.024) without any concomitant changes at the spinal level. These effects were still present 30min after the cessation of both interventions. There was no significant main effect of intervention, F(1,11)=0.38, p=0.550, indicating that the changes in MEP occurred independently of the type of afferent inflow. An afferent volley generated from a passive movement or an electrical stimulus arrives at the somatosensory cortex at similar times. It is thus likely that the similar effects observed here are strictly due to the tight coupling in time between the afferent inflow and the PN of the MRCP. This provides further support to the associative nature of the proposed BCI system.

An Associative Brain-Computer-Interface for Acute Stroke Patients

An efficient innovative Brain-Computer-Interface system that empowers chronic stroke patients to control an artificial activation of their lower limb muscle through task specific motor intent has been tested in the past. In the current study it was applied to acute stroke patients. The system consists in detecting the movement-related cortical potential (MRCP) using scalp electrodes as the patient attempts to perform a dorsiflexion task. This is translated into the control command for an electrical stimulator to generate a stimulus to the nerve that innervates and thus activates the prime mover (tibialis anterior). This activation is precisely and individually timed such that the sensory signal arising from the stimulation reaches the motor cortex during its maximum activation due to the intention. The output of the motor cortical area representing the dorsiflexor muscles was significantly enhanced in all patients tested following a single session of 30 repetitions. All patients were able to perform the intervention with minimal training and very few repetitions, making this a feasible new efficient approach for restoration of motor function in stroke patients. Such few necessary applications of the protocol make it a unique approach in comparison to available techniques and paves the way for at home use devices.

Short-latency crossed responses in the human biceps femoris muscle

The present study is the first to show short‐latency crossed‐spinal reflexes in the human upper leg muscles following mechanical rotations to the ipsilateral knee (iKnee) joint. The short‐latency reflex in the contralateral biceps femoris (cBF) was inhibitory following iKnee extension perturbations, and facilitatory following iKnee flexion perturbations. The onset latency was 44 ms, indicating that purely spinal pathways mediate the cBF reflexes. The short‐latency cBF inhibitory and facilitatory reflexes followed the automatic gain control principle, becoming larger as the level of background contraction in the cBF increased. The short‐latency cBF reflexes were observed at the motor unit level using i.m. electromyography recordings, and the same population of cBF motor units that was inhibited following iKnee extensions was facilitated following iKnee flexions. Parallel interneuronal pathways from ipsilateral afferents to common motoneurons in the contralateral leg can therefore probably explain the perturbation direction‐dependent reversal in the sign of the short‐latency cBF reflex.

Spinal plasticity in robot-mediated therapy for the lower limbs.

Robot-mediated therapy can help improve walking ability in patients following injuries to the central nervous system. However, the efficacy of this treatment varies between patients, and evidence for the mechanisms underlying functional improvements in humans is poor, particularly in terms of neural changes in the spinal cord. Here, we review the recent literature on spinal plasticity induced by robotic-based training in humans and propose recommendations for the measurement of spinal plasticity using robotic devices. Evidence for spinal plasticity in humans following robotic training is limited to the lower limbs. Body weight-supported (BWS) robotic-assisted step training of patients with spinal cord injury (SCI) or stroke patients has been shown to lead to changes in the amplitude and phase modulation of spinal reflex pathways elicited by electrical stimulation or joint rotations. Of particular importance is the finding that, among other changes to the spinal reflex circuitries, BWS robotic-assisted step training in SCI patients resulted in the re-emergence of a physiological phase modulation of the soleus H-reflex during walking. Stretch reflexes elicited by joint rotations constitute a tool of interest to probe spinal circuitry since the technology necessary to produce these perturbations could be integrated as a natural part of robotic devices. Presently, ad-hoc devices with an actuator capable of producing perturbations powerful enough to elicit the reflex are available but are not part of robotic devices used for training purposes. A further development of robotic devices that include the technology to elicit stretch reflexes would allow for the spinal circuitry to be routinely tested as a part of the training and evaluation protocols.

Paired Associative Stimulation Targeting the Tibialis Anterior Muscle using either Mono or Biphasic Transcranial Magnetic Stimulation

Paired associative stimulation (PAS) protocols induce plastic changes within the motor cortex. The objectives of this study were to investigate PAS effects targeting the tibialis anterior (TA) muscle using a biphasic transcranial magnetic stimulation (TMS) pulse form and, to determine whether a reduced intensity of this pulse would lead to significant changes as has been reported for hand muscles using a monophasic TMS pulse. Three interventions were investigated: (1) suprathreshold PAbi-PAS (n = 11); (2) suprathreshold PAmono-PAS (n = 11) where PAS was applied using a biphasic or monophasic pulse form at 120% resting motor threshold (RMT); (3) subthreshold PAbi-PAS (n = 10) where PAS was applied as for (1) at 95% active motor threshold (AMT). The peak-to-peak motor evoked potentials (MEPs) were quantified prior to, immediately following, and 30 min after the cessation of the intervention. TA MEP size increased significantly for all interventions immediately post (61% for suprathreshold PAbi-PAS, 83% for suprathreshold PAmono-PAS, 55% for subthreshold PAbi-PAS) and 30 min after the cessation of the intervention (123% for suprathreshold PAbi-PAS, 105% for suprathreshold PAmono-PAS, 80% for subthreshold PAbi-PAS. PAS using a biphasic pulse form at subthreshold intensities induces similar effects to conventional PAS.

Functionality of the contralateral biceps femoris reflex response during human walking

In this study we examined the functionality of the contralateral biceps femoris (cBF) reflex response following ipsilateral knee extension joint rotations during the late stance phase of the gait cycle [1]. Stevenson et al. [1] proposed that the cBF reflex acts to slow the forward progression of the body in order to maintain dynamic equilibrium during walking. Therefore, we hypothesized that if we suddenly slowed the treadmill participants were walking on, the cBF reflex would be inhibited because the necessity to break the forward progression of the body would be decreased. Conversely, if we suddenly sped up the treadmill, the breaking requirement would be greater and the cBF reflex would be larger. We found this to be the case when the treadmill velocity was suddenly changed either 100 ms or 50 ms prior to the onset of the ipsilateral knee perturbations. The cBF reflex was unchanged when the treadmill velocity was altered concurrently or 50 ms after knee perturbation onset. These results, together with the finding that the cBF reflex response is under some cortical control [1], strongly suggest a functional role for the cBF reflex during walking that is adaptable to the environmental situation.

Feed‐forward control of phonetic gestures in consonant–vowel syllables: Evidence from responses to auditory startle.

Speech production like other limb movements relies on both feed‐forward and feedback mechanisms. Use of a startling auditory stimulus (>90 dB) has been shown to trigger fast, accurate feed‐forward performances in upper limb movements prior to access to feedback information [Valls‐Sole et al. (1999), J. Physiol. 516: 931–938; Carlsen et al. (2004), J. Mot. Behav. 36: 253–264]. This startle paradigm is applied to test whether pre‐programed, feed‐forward speech production differs in phonetic detail from production with access to feedback. The experiment examined the production of the CV syllable [ba], starting with the mouth either open or closed. This speech production was triggered either by a control stimulus (82 dB) or by a startling stimulus (124 dB). Results from ten participants showed that lip compression occurred for both starting conditions (mouth open and mouth closed), and also indicated that the timing relationships of the articulators were stable across control trials and startle trials. The ac...